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Cancer-causing bacterium targets tumor-suppressor protein
Date:8/2/2010

tes different kinds of genes controlling cell growth and death," Chen said. "The first thing we wanted to see was whether H. pylori has any effect on the transcription activity of RUNX3."

Two graduate students in Chen's lab, Ying-Hung Nicole Tsang and Acacia Lamb, began the study by examining RUNX3 transcription activity in H. pylori-infected gastric epithelial cells. They found that infection with CagA-positive H. pylori inhibited the transcription activity of RUNX3 and reduced levels of the RUNX3 protein in cells. CagA-negative H. pylori had no effect on RUNX3 levels or activity.

"In fact, CagA alone is sufficient to down-regulate the RUNX3 transcription activity and reduce the expression of RUNX3, further supporting the importance of this bacterial protein in the genesis of gastric disease," Chen said.

Further tests revealed that CagA and RUNX3 physically interact with each other in human epithelial cells. The researchers found that a newly identified domain within CagA, the WW domain, recognizes a sequence in the RUNX3 protein known as the "PY motif." They further showed that this interaction leads to the "tagging" of RUNX3 for degradation via a process called ubiquitination.

Previous studies found that there are several unique sequences within the carboxyl-terminal region of CagA that are vital to the protein's ability to interact with host proteins and disrupt normal cellular processes.

"This is the first time anybody has identified a unique domain within the amino-terminal region of the CagA protein, and it will help us to better understand how this oncogenic protein functions," Chen said. "This study has uncovered a new step in the initiation of H. pylori-induced gastric cancer."

The accumulation of many deleterious changes in cells leads to the development of cancer. RUNX3 helps cells react when cellular processes go awry, so H. pylori-induced degradation of
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Contact: Diana Yates, Life Sciences Editor
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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